This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Maternal cigarette smoking has been associated with a variety of adverse fetal, infant, and childhood developmental outcomes. In the United States alone, approximately one million infants are exposed prenatally to cigarette smoke each year! Although maternal cigarette smoking during pregnancy is a well documented risk factor for low birth weight, with its attendant complications for infant/childhood development, a direct linkage between prenatal cigarette smoke exposure and postnatal neurobehavioral/cognitive impairment remains poorly defined. The global objective of the research program is to establish mouse-human experimental correlates to mechanistically investigate the neuroanatomical, cellular and molecular substrates underlying maternal cigarette smoking-induced defects in neuron/cognitive development. Since the hippocampus subserves a central role [unreadable]across species [unreadable] in neuro/cognition, especially in the information processing involved in learning and memory, the original central hypothesis under investigation was that maternal tobacco use during pregnancy interferes with the cellular and molecular ontogenesis of the hippocampus, resulting in altered hippocampus-dependent learning and memory in the offspring. The animal studies conducted under this research program employ a mouse model, established in our laboratory, in which developmental (gestational and early postnatal) inhalation exposure to cigarette smoke simulates human maternal smoking during pregnancy. The following hypotheses are being tested. Hypothesis #1: Tobacco smoke exposure during development, in a murine model simulating human maternal cigarette smoking during pregnancy, results in neurobehavioral abnormalities involving hippocampus-dependent learning and memory. Hypothesis #2: Alterations in the establishment of normal cytoarchitecture and neurogenesis in the murine hippocampus are elicited by exposure to tobacco smoke during development, in the absence of attendant effects on murine fetal/neonatal growth. Hypothesis #3: Tobacco smoke exposure during development results in hippocampal, neuronal subtype-specific alterations in the expression of genes during murine ontogenesis that are critical mediators of neuronal developmental plasticity, learning and memory.